Does progesterone inhibit bacteria-stimulated interleukin-8 production by lower genital tract epithelial cells?

OBJECTIVE Progesterone (P(4)) has been clinically shown to prevent the recurrence of preterm birth. The mechanism(s) of action is unclear, but may involve modulation of the immunologic inflammatory response of the lower genital tract. We evaluated the effects of P(4) on interleukin-8 (IL-8) production by vaginal and cervical epithelial cells stimulated with bacterial species that are commonly associated with preterm birth. METHODS Vaginal and endocervical epithelial cells were incubated with up to 10,000 ng/mL P(4) overnight and stimulated with heat-killed Escherichia coli, Gardnerella vaginalis, or Ureaplasma urealyticum. Concentrations of IL-8 in conditioned medium were quantified by ELISA and viability of the cell cultures was measured by the reduction of a tetrazolium salt. RESULTS E. coli, G. vaginalis and U. urealyticum-stimulated IL-8 production for both cell lines. P(4) inhibited basal and bacteria-stimulated IL-8 production for vaginal epithelial cells but enhanced IL-8 production by endocervical cells. P(4) reduced the number of viable cells for both cell lines. CONCLUSIONS P(4) inhibits IL-8 production by vaginal epithelial cells stimulated with pathogens associated with preterm birth, possibly by reducing the number of viable cells or by inhibiting their proliferation. Although P(4) also reduces proliferation of endocervical cells it also increases their production of IL-8.